CN1167437A - 用三芳基-乙烯衍生物治疗和预防骨质疏松的方法 - Google Patents
用三芳基-乙烯衍生物治疗和预防骨质疏松的方法 Download PDFInfo
- Publication number
- CN1167437A CN1167437A CN95196510A CN95196510A CN1167437A CN 1167437 A CN1167437 A CN 1167437A CN 95196510 A CN95196510 A CN 95196510A CN 95196510 A CN95196510 A CN 95196510A CN 1167437 A CN1167437 A CN 1167437A
- Authority
- CN
- China
- Prior art keywords
- ethylene
- phenyl
- chloro
- diphenyl
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 43
- 208000001132 Osteoporosis Diseases 0.000 title claims abstract description 37
- 238000011282 treatment Methods 0.000 title claims abstract description 23
- 230000002265 prevention Effects 0.000 title abstract description 11
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 45
- 150000001875 compounds Chemical class 0.000 claims description 285
- 229910052801 chlorine Inorganic materials 0.000 claims description 65
- 239000000460 chlorine Substances 0.000 claims description 62
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 61
- 229910052739 hydrogen Inorganic materials 0.000 claims description 55
- 239000001257 hydrogen Substances 0.000 claims description 55
- 229910052760 oxygen Inorganic materials 0.000 claims description 43
- 150000003839 salts Chemical class 0.000 claims description 32
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 31
- 229910052794 bromium Chemical group 0.000 claims description 30
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 229910052736 halogen Inorganic materials 0.000 claims description 28
- 150000002431 hydrogen Chemical class 0.000 claims description 27
- 150000002367 halogens Chemical class 0.000 claims description 26
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 17
- 230000001009 osteoporotic effect Effects 0.000 claims description 17
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 11
- UTYMHSHRSOOSEY-BYYHNAKLSA-N 4-[4-[(e)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethylbutan-1-amine Chemical group C1=CC(OCCCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 UTYMHSHRSOOSEY-BYYHNAKLSA-N 0.000 claims description 5
- UTYMHSHRSOOSEY-DQSJHHFOSA-N 4-[4-[(z)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethylbutan-1-amine Chemical group C1=CC(OCCCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(/Cl)C1=CC=CC=C1 UTYMHSHRSOOSEY-DQSJHHFOSA-N 0.000 claims description 2
- ZWLVFXJIEKRSKO-QPLCGJKRSA-N C1=CC(NCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(/Cl)C1=CC=CC=C1 Chemical group C1=CC(NCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(/Cl)C1=CC=CC=C1 ZWLVFXJIEKRSKO-QPLCGJKRSA-N 0.000 claims 1
- ZWLVFXJIEKRSKO-OCEACIFDSA-N n-[4-[(e)-2-chloro-1,2-diphenylethenyl]phenyl]-n',n'-diethylethane-1,2-diamine Chemical group C1=CC(NCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 ZWLVFXJIEKRSKO-OCEACIFDSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 131
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 117
- 239000005977 Ethylene Substances 0.000 description 112
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 109
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 77
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 72
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 72
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 69
- 239000000203 mixture Substances 0.000 description 69
- 239000007787 solid Substances 0.000 description 69
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 66
- 238000007738 vacuum evaporation Methods 0.000 description 64
- 239000000243 solution Substances 0.000 description 62
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- 239000012044 organic layer Substances 0.000 description 58
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
- -1 normal-butyl Chemical group 0.000 description 54
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 52
- 239000000376 reactant Substances 0.000 description 51
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 48
- 238000004587 chromatography analysis Methods 0.000 description 45
- 239000002585 base Substances 0.000 description 43
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
- 235000015165 citric acid Nutrition 0.000 description 39
- 239000001301 oxygen Substances 0.000 description 37
- 239000000741 silica gel Substances 0.000 description 37
- 229910002027 silica gel Inorganic materials 0.000 description 37
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 36
- 238000002360 preparation method Methods 0.000 description 36
- 239000000047 product Substances 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- 238000001035 drying Methods 0.000 description 31
- 239000002904 solvent Substances 0.000 description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 27
- 238000001914 filtration Methods 0.000 description 26
- 235000002639 sodium chloride Nutrition 0.000 description 26
- 238000000746 purification Methods 0.000 description 23
- 238000001953 recrystallisation Methods 0.000 description 23
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 22
- 238000004128 high performance liquid chromatography Methods 0.000 description 22
- 238000010992 reflux Methods 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000000284 extract Substances 0.000 description 21
- 235000011121 sodium hydroxide Nutrition 0.000 description 20
- VVFIZEWCXRQNGK-UHFFFAOYSA-N (1-chloro-2-phenylethenyl)benzene Chemical group C=1C=CC=CC=1C(Cl)=CC1=CC=CC=C1 VVFIZEWCXRQNGK-UHFFFAOYSA-N 0.000 description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- 239000002253 acid Substances 0.000 description 18
- 239000007864 aqueous solution Substances 0.000 description 18
- RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 description 18
- 238000005516 engineering process Methods 0.000 description 17
- 239000000463 material Substances 0.000 description 17
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
- 239000003513 alkali Substances 0.000 description 13
- 229910052799 carbon Inorganic materials 0.000 description 13
- 238000003810 ethyl acetate extraction Methods 0.000 description 13
- 239000010410 layer Substances 0.000 description 13
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 13
- 239000000546 pharmaceutical excipient Substances 0.000 description 13
- 125000006239 protecting group Chemical group 0.000 description 13
- 229920006395 saturated elastomer Polymers 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 238000010511 deprotection reaction Methods 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 12
- 238000003809 water extraction Methods 0.000 description 12
- NHNUFAASKXPOQA-UHFFFAOYSA-N (3-acetamido-2-hydroxyphenyl)arsonic acid Chemical compound C(C)(=O)NC=1C(=C(C=CC1)[As](O)(=O)O)O NHNUFAASKXPOQA-UHFFFAOYSA-N 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 150000001412 amines Chemical class 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- 230000008020 evaporation Effects 0.000 description 11
- 238000000605 extraction Methods 0.000 description 11
- 238000011010 flushing procedure Methods 0.000 description 11
- 241000700159 Rattus Species 0.000 description 10
- 125000000217 alkyl group Chemical group 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 238000001291 vacuum drying Methods 0.000 description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- 238000013019 agitation Methods 0.000 description 9
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 9
- 239000012965 benzophenone Substances 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 8
- 239000007795 chemical reaction product Substances 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- 229910052708 sodium Inorganic materials 0.000 description 8
- 229910000029 sodium carbonate Inorganic materials 0.000 description 8
- RBKHNGHPZZZJCI-UHFFFAOYSA-N (4-aminophenyl)-phenylmethanone Chemical compound C1=CC(N)=CC=C1C(=O)C1=CC=CC=C1 RBKHNGHPZZZJCI-UHFFFAOYSA-N 0.000 description 7
- 102000004067 Osteocalcin Human genes 0.000 description 7
- 108090000573 Osteocalcin Proteins 0.000 description 7
- 239000003638 chemical reducing agent Substances 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 125000003047 N-acetyl group Chemical group 0.000 description 6
- 235000019270 ammonium chloride Nutrition 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 150000001721 carbon Chemical group 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- NIDSRGCVYOEDFW-UHFFFAOYSA-N 1-bromo-4-chlorobutane Chemical compound ClCCCCBr NIDSRGCVYOEDFW-UHFFFAOYSA-N 0.000 description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 239000012141 concentrate Substances 0.000 description 5
- 235000008504 concentrate Nutrition 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 210000002303 tibia Anatomy 0.000 description 5
- 210000000689 upper leg Anatomy 0.000 description 5
- SBYMUDUGTIKLCR-UHFFFAOYSA-N 2-chloroethenylbenzene Chemical group ClC=CC1=CC=CC=C1 SBYMUDUGTIKLCR-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 230000031709 bromination Effects 0.000 description 4
- 238000005893 bromination reaction Methods 0.000 description 4
- 125000001246 bromo group Chemical group Br* 0.000 description 4
- 238000005660 chlorination reaction Methods 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 4
- SCEZYJKGDJPHQO-UHFFFAOYSA-M magnesium;methanidylbenzene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C1=CC=CC=C1 SCEZYJKGDJPHQO-UHFFFAOYSA-M 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 238000002601 radiography Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- PIQUQCCWGGFRPS-UHFFFAOYSA-N 1-(2,2-diphenylethenyl)-3-methoxybenzene Chemical group C1(=CC=CC=C1)C(=CC1=CC(=CC=C1)OC)C1=CC=CC=C1 PIQUQCCWGGFRPS-UHFFFAOYSA-N 0.000 description 3
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 3
- AMKGTHFGXVUJGG-RXQWRGDBSA-N 4-[4-[(e)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethylbutan-1-amine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1=CC(OCCCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 AMKGTHFGXVUJGG-RXQWRGDBSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 3
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000021736 acetylation Effects 0.000 description 3
- 238000006640 acetylation reaction Methods 0.000 description 3
- 125000001118 alkylidene group Chemical group 0.000 description 3
- 229940073608 benzyl chloride Drugs 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 150000003053 piperidines Chemical class 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 238000003127 radioimmunoassay Methods 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229960002317 succinimide Drugs 0.000 description 3
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- QMPKJVBRCQVFLL-UHFFFAOYSA-N 1,1,2-triphenylethanol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(O)CC1=CC=CC=C1 QMPKJVBRCQVFLL-UHFFFAOYSA-N 0.000 description 2
- PPOUBMWEPNDEES-UHFFFAOYSA-N 1-(4-aminophenyl)-1,2-diphenylethanol Chemical compound C1=CC(N)=CC=C1C(O)(C=1C=CC=CC=1)CC1=CC=CC=C1 PPOUBMWEPNDEES-UHFFFAOYSA-N 0.000 description 2
- SNQDKIRKUMJBQS-KXYMVQBMSA-N 12-[4-[(z)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethyldodecan-1-amine Chemical group C1=CC(OCCCCCCCCCCCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(/Cl)C1=CC=CC=C1 SNQDKIRKUMJBQS-KXYMVQBMSA-N 0.000 description 2
- YMDNODNLFSHHCV-UHFFFAOYSA-N 2-chloro-n,n-diethylethanamine Chemical compound CCN(CC)CCCl YMDNODNLFSHHCV-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- UTYMHSHRSOOSEY-UHFFFAOYSA-N 4-[4-(2-chloro-1,2-diphenylethenyl)phenoxy]-N,N-diethylbutan-1-amine Chemical group C1=CC(OCCCCN(CC)CC)=CC=C1C(C=1C=CC=CC=1)=C(Cl)C1=CC=CC=C1 UTYMHSHRSOOSEY-UHFFFAOYSA-N 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- XWMIYYSYKYTDTE-UHFFFAOYSA-N 5-[4-(2-chloro-1,2-diphenylethenyl)phenoxy]-n,n-diethylpentan-1-amine Chemical group C1=CC(OCCCCCN(CC)CC)=CC=C1C(C=1C=CC=CC=1)=C(Cl)C1=CC=CC=C1 XWMIYYSYKYTDTE-UHFFFAOYSA-N 0.000 description 2
- PEKBOSQAPYHILJ-QNEJGDQOSA-N 8-[4-[(e)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethyloctan-1-amine Chemical group C1=CC(OCCCCCCCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 PEKBOSQAPYHILJ-QNEJGDQOSA-N 0.000 description 2
- PEKBOSQAPYHILJ-MVJHLKBCSA-N 8-[4-[(z)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethyloctan-1-amine Chemical group C1=CC(OCCCCCCCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(/Cl)C1=CC=CC=C1 PEKBOSQAPYHILJ-MVJHLKBCSA-N 0.000 description 2
- 208000010392 Bone Fractures Diseases 0.000 description 2
- 206010065687 Bone loss Diseases 0.000 description 2
- GCQKDKKYPLJRCW-UHFFFAOYSA-N C1C(=O)OC(C(OC(=O)CC1(C(=O)O)O)(C2=CC=CC=C2)Cl)C3=CC=CC=C3 Chemical compound C1C(=O)OC(C(OC(=O)CC1(C(=O)O)O)(C2=CC=CC=C2)Cl)C3=CC=CC=C3 GCQKDKKYPLJRCW-UHFFFAOYSA-N 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 208000035126 Facies Diseases 0.000 description 2
- 206010017076 Fracture Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- OBXSGRKNCOCTTM-UHFFFAOYSA-N benzyl diethyl phosphate Chemical compound CCOP(=O)(OCC)OCC1=CC=CC=C1 OBXSGRKNCOCTTM-UHFFFAOYSA-N 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- SNCZNSNPXMPCGN-UHFFFAOYSA-N butanediamide Chemical compound NC(=O)CCC(N)=O SNCZNSNPXMPCGN-UHFFFAOYSA-N 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 238000009806 oophorectomy Methods 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 2
- 235000011007 phosphoric acid Nutrition 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229920001084 poly(chloroprene) Polymers 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 108010048734 sclerotin Proteins 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 210000004872 soft tissue Anatomy 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
- QEQFTTCZLHLKFX-UHFFFAOYSA-N (1-chloro-2,2-diphenylethenyl)benzene Chemical group C=1C=CC=CC=1C(Cl)=C(C=1C=CC=CC=1)C1=CC=CC=C1 QEQFTTCZLHLKFX-UHFFFAOYSA-N 0.000 description 1
- WWMFRKPUQJRNBY-UHFFFAOYSA-N (2,3-dimethoxyphenyl)-phenylmethanone Chemical compound COC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1OC WWMFRKPUQJRNBY-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- KFZOPAKKTMEFEY-UHFFFAOYSA-N 1-[1-[4-(diethylamino)butoxy]cyclohexa-2,4-dien-1-yl]-1,2-diphenylethanol;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1CC(O)(C=1C=CC=CC=1)C1(OCCCCN(CC)CC)CC=CC=C1 KFZOPAKKTMEFEY-UHFFFAOYSA-N 0.000 description 1
- PHHNNDKXQVKJEP-UHFFFAOYSA-N 1-bromo-5-chloropentane Chemical compound ClCCCCCBr PHHNNDKXQVKJEP-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- RJYNIRBKRJAXGR-UHFFFAOYSA-N 10-(diethylamino)decan-1-ol Chemical compound CCN(CC)CCCCCCCCCCO RJYNIRBKRJAXGR-UHFFFAOYSA-N 0.000 description 1
- ZHPYVBBUJYVKCB-UHFFFAOYSA-N 12-(diethylamino)dodecan-1-ol Chemical compound CCN(CC)CCCCCCCCCCCCO ZHPYVBBUJYVKCB-UHFFFAOYSA-N 0.000 description 1
- SNQDKIRKUMJBQS-ULDVOPSXSA-N 12-[4-[(e)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethyldodecan-1-amine Chemical group C1=CC(OCCCCCCCCCCCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 SNQDKIRKUMJBQS-ULDVOPSXSA-N 0.000 description 1
- HSPDZQMIIFYPPU-XPPFCZECSA-N 12-[4-[(z)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethyldodecan-1-amine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1=CC(OCCCCCCCCCCCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(/Cl)C1=CC=CC=C1 HSPDZQMIIFYPPU-XPPFCZECSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- PKRSYEPBQPFNRB-UHFFFAOYSA-N 2-phenoxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1OC1=CC=CC=C1 PKRSYEPBQPFNRB-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 1
- AMKGTHFGXVUJGG-LXCLTORNSA-N 4-[4-[(z)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethylbutan-1-amine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1=CC(OCCCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(/Cl)C1=CC=CC=C1 AMKGTHFGXVUJGG-LXCLTORNSA-N 0.000 description 1
- CDIIZULDSLKBKV-UHFFFAOYSA-N 4-chlorobutanoyl chloride Chemical compound ClCCCC(Cl)=O CDIIZULDSLKBKV-UHFFFAOYSA-N 0.000 description 1
- XWMIYYSYKYTDTE-ZQHSETAFSA-N 5-[4-[(e)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethylpentan-1-amine Chemical group C1=CC(OCCCCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 XWMIYYSYKYTDTE-ZQHSETAFSA-N 0.000 description 1
- PXIJJFNYDCXSPN-IRWWKPKRSA-N 5-[4-[(e)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethylpentan-1-amine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1=CC(OCCCCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 PXIJJFNYDCXSPN-IRWWKPKRSA-N 0.000 description 1
- XWMIYYSYKYTDTE-ZIADKAODSA-N 5-[4-[(z)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethylpentan-1-amine Chemical group C1=CC(OCCCCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(/Cl)C1=CC=CC=C1 XWMIYYSYKYTDTE-ZIADKAODSA-N 0.000 description 1
- PXIJJFNYDCXSPN-FJBFXRHMSA-N 5-[4-[(z)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethylpentan-1-amine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1=CC(OCCCCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(/Cl)C1=CC=CC=C1 PXIJJFNYDCXSPN-FJBFXRHMSA-N 0.000 description 1
- YLNQOWCLZJQJLN-UHFFFAOYSA-N 6-(diethylamino)hexan-1-ol Chemical compound CCN(CC)CCCCCCO YLNQOWCLZJQJLN-UHFFFAOYSA-N 0.000 description 1
- GSOCJUZWVQNJDY-QVIHXGFCSA-N 6-[4-[(e)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethylhexan-1-amine Chemical group C1=CC(OCCCCCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GSOCJUZWVQNJDY-QVIHXGFCSA-N 0.000 description 1
- DFXHEDQDAZIQKM-BXGDTPBJSA-N 6-[4-[(e)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethylhexan-1-amine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1=CC(OCCCCCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 DFXHEDQDAZIQKM-BXGDTPBJSA-N 0.000 description 1
- GSOCJUZWVQNJDY-FLWNBWAVSA-N 6-[4-[(z)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethylhexan-1-amine Chemical group C1=CC(OCCCCCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(/Cl)C1=CC=CC=C1 GSOCJUZWVQNJDY-FLWNBWAVSA-N 0.000 description 1
- DFXHEDQDAZIQKM-DHKWPOFJSA-N 6-[4-[(z)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethylhexan-1-amine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1=CC(OCCCCCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(/Cl)C1=CC=CC=C1 DFXHEDQDAZIQKM-DHKWPOFJSA-N 0.000 description 1
- YKEUKJROCLHMNK-VLSXRWFESA-N 8-[4-[(z)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethyloctan-1-amine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1=CC(OCCCCCCCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(/Cl)C1=CC=CC=C1 YKEUKJROCLHMNK-VLSXRWFESA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 101100049849 Arabidopsis thaliana XK1 gene Proteins 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- HSPDZQMIIFYPPU-KPYQYLATSA-N C(CC(O)(C(=O)O)CC(=O)O)(=O)O.C(C)N(CCCCCCCCCCCCOC1=CC=C(C=C1)\C(=C(\Cl)/C1=CC=CC=C1)\C1=CC=CC=C1)CC Chemical compound C(CC(O)(C(=O)O)CC(=O)O)(=O)O.C(C)N(CCCCCCCCCCCCOC1=CC=C(C=C1)\C(=C(\Cl)/C1=CC=CC=C1)\C1=CC=CC=C1)CC HSPDZQMIIFYPPU-KPYQYLATSA-N 0.000 description 1
- YKEUKJROCLHMNK-MRRLHAJBSA-N C(CC(O)(C(=O)O)CC(=O)O)(=O)O.C(C)N(CCCCCCCCOC1=CC=C(C=C1)\C(=C(\Cl)/C1=CC=CC=C1)\C1=CC=CC=C1)CC Chemical compound C(CC(O)(C(=O)O)CC(=O)O)(=O)O.C(C)N(CCCCCCCCOC1=CC=C(C=C1)\C(=C(\Cl)/C1=CC=CC=C1)\C1=CC=CC=C1)CC YKEUKJROCLHMNK-MRRLHAJBSA-N 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 208000014311 Cushing syndrome Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 206010025476 Malabsorption Diseases 0.000 description 1
- 208000004155 Malabsorption Syndromes Diseases 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000002903 Thalassemia Diseases 0.000 description 1
- GWSRIUFFKGTYNR-UHFFFAOYSA-N [4-[4-(diethylamino)butoxy]phenyl]-phenylmethanone Chemical compound C1=CC(OCCCCN(CC)CC)=CC=C1C(=O)C1=CC=CC=C1 GWSRIUFFKGTYNR-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000005377 adsorption chromatography Methods 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000006242 amine protecting group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- OCBHHZMJRVXXQK-UHFFFAOYSA-M benzyl-dimethyl-tetradecylazanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 OCBHHZMJRVXXQK-UHFFFAOYSA-M 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 230000037182 bone density Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- KBPLFHHGFOOTCA-UHFFFAOYSA-N caprylic alcohol Natural products CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- YDVNLQGCLLPHAH-UHFFFAOYSA-N dichloromethane;hydrate Chemical compound O.ClCCl YDVNLQGCLLPHAH-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000003194 forelimb Anatomy 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 210000004349 growth plate Anatomy 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910001386 lithium phosphate Inorganic materials 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 230000009245 menopause Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- YWOITFUKFOYODT-UHFFFAOYSA-N methanol;sodium Chemical compound [Na].OC YWOITFUKFOYODT-UHFFFAOYSA-N 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- ZWRUINPWMLAQRD-UHFFFAOYSA-N n-Nonyl alcohol Natural products CCCCCCCCCO ZWRUINPWMLAQRD-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 210000002990 parathyroid gland Anatomy 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 229960002668 sodium chloride Drugs 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- PESXGULMKCKJCC-UHFFFAOYSA-M sodium;4-methoxycarbonylphenolate Chemical compound [Na+].COC(=O)C1=CC=C([O-])C=C1 PESXGULMKCKJCC-UHFFFAOYSA-M 0.000 description 1
- IXMINYBUNCWGER-UHFFFAOYSA-M sodium;4-propoxycarbonylphenolate Chemical compound [Na+].CCCOC(=O)C1=CC=C([O-])C=C1 IXMINYBUNCWGER-UHFFFAOYSA-M 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-N sodium;sulfurous acid Chemical compound [Na+].OS(O)=O DWAQJAXMDSEUJJ-UHFFFAOYSA-N 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 206010041569 spinal fracture Diseases 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000003930 superacid Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 208000005057 thyrotoxicosis Diseases 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 150000003628 tricarboxylic acids Chemical class 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- TWQULNDIKKJZPH-UHFFFAOYSA-K trilithium;phosphate Chemical compound [Li+].[Li+].[Li+].[O-]P([O-])([O-])=O TWQULNDIKKJZPH-UHFFFAOYSA-K 0.000 description 1
- 238000006886 vinylation reaction Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XOSXWYQMOYSSKB-LDKJGXKFSA-L water blue Chemical compound CC1=CC(/C(\C(C=C2)=CC=C2NC(C=C2)=CC=C2S([O-])(=O)=O)=C(\C=C2)/C=C/C\2=N\C(C=C2)=CC=C2S([O-])(=O)=O)=CC(S(O)(=O)=O)=C1N.[Na+].[Na+] XOSXWYQMOYSSKB-LDKJGXKFSA-L 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/136—Amines having aromatic rings, e.g. ketamine, nortriptyline having the amino group directly attached to the aromatic ring, e.g. benzeneamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34611194A | 1994-11-29 | 1994-11-29 | |
| US08/346,111 | 1994-11-29 | ||
| US08/531,885 | 1995-10-11 | ||
| US08/531,885 US5691384A (en) | 1994-11-29 | 1995-10-11 | Method of using triaryl-ethylene derivatives in the treatment and prevention of osteoporosis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1167437A true CN1167437A (zh) | 1997-12-10 |
Family
ID=26994698
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN95196510A Pending CN1167437A (zh) | 1994-11-29 | 1995-10-27 | 用三芳基-乙烯衍生物治疗和预防骨质疏松的方法 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US5693674A (no) |
| EP (1) | EP0794771A1 (no) |
| JP (1) | JPH10509962A (no) |
| CN (1) | CN1167437A (no) |
| AU (1) | AU707290B2 (no) |
| CA (1) | CA2206422A1 (no) |
| FI (1) | FI972235A0 (no) |
| HU (1) | HUT77603A (no) |
| IL (1) | IL116142A0 (no) |
| MX (1) | MX9703944A (no) |
| NO (1) | NO972426L (no) |
| WO (1) | WO1996016646A1 (no) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6465445B1 (en) | 1998-06-11 | 2002-10-15 | Endorecherche, Inc. | Medical uses of a selective estrogen receptor modulator in combination with sex steroid precursors |
| US7005428B1 (en) | 1998-06-11 | 2006-02-28 | Endorecherche, Inc. | Medical uses of a selective estrogen receptor modulator in combination with sex steroid precursors |
| TW593256B (en) | 1999-11-16 | 2004-06-21 | Hormos Medical Oy Ltd | Triphenylalkene derivatives and their use as selective estrogen receptor modulators |
| US20040248989A1 (en) | 2003-06-05 | 2004-12-09 | Risto Santti | Method for the treatment or prevention of lower urinary tract symptoms |
| CN101448490A (zh) * | 2006-05-22 | 2009-06-03 | 霍尔莫斯医疗有限公司 | 治疗慢性非细菌性前列腺炎的选择性雌激素受体调节剂或者芳香酶抑制剂 |
| EP2121553B1 (en) * | 2007-02-14 | 2012-06-27 | Hormos Medical Ltd. | Method for the preparation of therapeutically valuable triphenylbutene derivatives |
| US7504530B2 (en) * | 2007-02-14 | 2009-03-17 | Hormos Medical Ltd. | Methods for the preparation of fispemifene from ospemifene |
| EP2307342B1 (en) | 2008-07-02 | 2017-06-21 | British Columbia Cancer Agency Branch | Diglycidic ether derivative therapeutics and methods for their use |
| JP6174156B2 (ja) | 2012-10-19 | 2017-08-02 | フェルミオン オサケ ユキチュア | オスペミフェンの製造方法 |
| WO2016112455A1 (en) * | 2015-01-13 | 2016-07-21 | British Columbia Cancer Agency Branch | Heterocyclic compounds for cancer imaging and treatment and methods for their use |
| US10471023B2 (en) | 2015-03-12 | 2019-11-12 | British Columbia Cancer Agency Branch | Bisphenol ether derivatives and methods for using the same |
| US20170298033A1 (en) | 2016-04-15 | 2017-10-19 | The University Of British Columbia | Bisphenol derivatives and their use as androgen receptor activity modulators |
| US11485713B2 (en) | 2018-05-25 | 2022-11-01 | Essa Pharma, Inc. | Androgen receptor modulators and methods for their use |
| CA3115101A1 (en) | 2018-10-18 | 2020-04-23 | Essa Pharma, Inc. | Androgen receptor modulators and methods for their use |
| WO2020198712A1 (en) | 2019-03-28 | 2020-10-01 | Essa Pharma, Inc. | Pharmaceutical compositions and combinations comprising inhibitors of the androgen receptor and uses thereof |
| EP4135675A4 (en) | 2020-04-17 | 2024-04-10 | Essa Pharma, Inc. | SOLID FORMS OF AN N-TERMINAL DOMAIN ANDROGEN RECEPTOR INHIBITOR AND USES THEREOF |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2914563A (en) * | 1957-08-06 | 1959-11-24 | Wm S Merrell Co | Therapeutic composition |
| GB1013907A (en) * | 1962-09-13 | 1965-12-22 | Ici Ltd | Alkene derivatives |
| US3247252A (en) * | 1962-11-14 | 1966-04-19 | Richardson Merrell Inc | Beta-dialkylaminoethylamino-triphenylethanols, -ethanes, and -ethenes |
| GB1099093A (en) * | 1965-09-03 | 1968-01-17 | Ici Ltd | Alkene derivatives |
| GB1128379A (en) * | 1966-06-20 | 1968-09-25 | Ici Ltd | Novel alkene derivatives, process for the preparation thereof and compositions containing the same |
| US4001229A (en) * | 1974-04-04 | 1977-01-04 | Mead Johnson & Company | Alkanesulfonamido triphenylethylenes |
| DE2860900D1 (en) * | 1977-08-22 | 1981-11-05 | Ici Plc | Triphenylalkene derivatives, process for their preparation and pharmaceutical compositions containing them |
| US4729999A (en) * | 1984-10-12 | 1988-03-08 | Bcm Technologies | Antiestrogen therapy for symptoms of estrogen deficiency |
| US4970237A (en) * | 1987-03-20 | 1990-11-13 | Yale University | Use of clomiphene to increase bone mass in premenopausal women |
| JPH06312930A (ja) * | 1993-04-30 | 1994-11-08 | Kuraray Co Ltd | 骨粗鬆症治療剤 |
| US5525633A (en) * | 1993-09-24 | 1996-06-11 | Merrell Dow Pharmaceuticals Inc. | Triaryl-ethylene derivatives |
| NZ272608A (en) * | 1994-07-22 | 2000-05-26 | Lilly Co Eli | Inhibiting bone loss by administering a bisphosphonate and a second compound selected from various compounds, including 2-phenyl-3-aroylbenzothienes; bisphosphonate combination salts |
-
1995
- 1995-10-27 EP EP95940561A patent/EP0794771A1/en not_active Withdrawn
- 1995-10-27 JP JP8517877A patent/JPH10509962A/ja active Pending
- 1995-10-27 WO PCT/US1995/013873 patent/WO1996016646A1/en not_active Application Discontinuation
- 1995-10-27 CA CA002206422A patent/CA2206422A1/en not_active Abandoned
- 1995-10-27 AU AU41967/96A patent/AU707290B2/en not_active Ceased
- 1995-10-27 MX MX9703944A patent/MX9703944A/es unknown
- 1995-10-27 CN CN95196510A patent/CN1167437A/zh active Pending
- 1995-10-27 HU HU9702022A patent/HUT77603A/hu unknown
- 1995-11-27 IL IL11614295A patent/IL116142A0/xx unknown
-
1996
- 1996-06-12 US US08/662,092 patent/US5693674A/en not_active Expired - Fee Related
-
1997
- 1997-05-27 FI FI972235A patent/FI972235A0/fi unknown
- 1997-05-28 NO NO972426A patent/NO972426L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| MX9703944A (es) | 1998-05-31 |
| JPH10509962A (ja) | 1998-09-29 |
| IL116142A0 (en) | 1996-01-31 |
| WO1996016646A1 (en) | 1996-06-06 |
| AU707290B2 (en) | 1999-07-08 |
| HUT77603A (hu) | 1998-06-29 |
| NO972426L (no) | 1997-07-29 |
| NO972426D0 (no) | 1997-05-28 |
| CA2206422A1 (en) | 1996-06-06 |
| US5693674A (en) | 1997-12-02 |
| FI972235A (fi) | 1997-05-27 |
| AU4196796A (en) | 1996-06-19 |
| FI972235A0 (fi) | 1997-05-27 |
| EP0794771A1 (en) | 1997-09-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1167437A (zh) | 用三芳基-乙烯衍生物治疗和预防骨质疏松的方法 | |
| CN1045768C (zh) | 一种血管紧张肽ⅱ拮抗剂化合物及其制备方法和用途 | |
| CN1084743C (zh) | 毒蕈碱拮抗剂 | |
| CN1207288C (zh) | 逆病毒蛋白酶抑制化合物 | |
| CN1170538C (zh) | 供治疗关节病的法呢基(Farnesyl)蛋白质转移酶抑制剂 | |
| CN1037440C (zh) | 血管紧张素ⅱ受体阻断剂2,3,6取代的喹唑啉酮的制造方法 | |
| CN1147471C (zh) | 肾素抑制剂 | |
| CN1832742A (zh) | 用于治疗心血管疾病的血管紧张素ii受体阻断剂氯沙坦、缬沙坦、坎地沙坦、替米沙坦、依普罗沙坦和奥美沙坦的硝基氧基衍生物 | |
| CN1168631A (zh) | 治疗抗性肿瘤的方法 | |
| CN1234738A (zh) | 奥氮平二水合物d | |
| CN1934091A (zh) | 治疗神经变性障碍的咪唑化合物 | |
| CN1056494A (zh) | 血小板激活因子的双芳基酰胺和脲拮抗剂 | |
| CN1267432C (zh) | 2－吡啶基－6,7,8,9－四氢嘧啶并[1,2－a]嘧啶－4－酮和7－吡啶基－2,3－二氢咪唑并[1,2－a]嘧啶－5(1H)酮衍生物 | |
| CN101068798A (zh) | 1－环丙基甲基－4－[2－(3,3,5,5－四甲基环己基)苯基]哌嗪的盐及结晶 | |
| CN1291978A (zh) | 作为整联蛋白拮抗剂的间－氮杂环氨基苯甲酸化合物及其衍生物 | |
| CN1229335C (zh) | 莫维诺林衍生物 | |
| CN1304401A (zh) | calcilytic化合物 | |
| CN1516580A (zh) | 磺酰胺类 | |
| CN1111986A (zh) | 治疗肠应激综合症的异噁唑衍生物 | |
| CN1331674A (zh) | 磺酰胺异羟肟酸酯 | |
| CN1809570A (zh) | [1,2,4]三唑并[1,5－a]嘧啶－2－基脲衍生物及其用途 | |
| CN1112364A (zh) | 哌嗪衍生物及其盐 | |
| CN1198158A (zh) | 作为酪氨酸激酶抑制剂的双环4－芳烷基氨基嘧啶衍生物 | |
| CN1703394A (zh) | 脂肪醇的碱性酯及它们作为抗炎药或免疫调节剂的用途 | |
| CN100340572C (zh) | 新的lhrh拮抗剂 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |